Tirzepatide (TZP) is a novel once-weekly dual GIP and GLP-1 receptor agonist evaluated in patients with type 2 diabetes (T2D) . Five Phase 3 SURPASS (S) trials have demonstrated safety and shown robust efficacy of TZP in improvement of glycaemic control and body weight (BW) in adults with T2D. To understand whether the weight-lowering effects of TZP are dependent on baseline BMI, we conducted subgroup analyses of S-1 through -5. BW change in the BMI subgroups (Subgroup 1 [<27 or ≥27 kg/m2] and Subgroup 2 [<30; ≥30 to <35; ≥35 kg/m2]) at primary endpoint was assessed in patients while on treatment without rescue medication (efficacy estimand) in the modified intention-to-treat (mITT) population, defined as all randomized patients who received at least one dose of study drug. All TZP doses (5, 10, 15 mg) lowered BW in patients with T2D irrespective of baseline BMI in both subgroups (p<0.001) . The weight reductions were generally dose-dependent and absolute weight change was generally greater in higher BMI categories. TZP-treated patients with T2D experienced weight loss across a spectrum of mean baseline BMI values in S-1 through -5 studies. The most frequent adverse events were GI-related events that were mild to moderate in severity and occurred during the dose-escalation period.


A.Kwan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.M.Maldonado: Employee; Eli Lilly and Company. H.Wang: None. N.Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. J.Wilding: Advisory Panel; Alnylam Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Mundipharma, Novo Nordisk A/S, Rhythm Pharmaceuticals, Inc., Sanofi, Research Support; AstraZeneca, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Takeda Pharmaceutical Company Limited.


Eli Lilly and Company

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